Hyperthermia is currently being evaluated as a potential cancer treatment modality. The mechanism(s) of hyperthermia killing and the induction of thermal resistance (thermotolerance) are not known. We will examine the role of the cellular reduction potential during and after heating to determine its role or alteration during thermal stress. This will be accomplished by using drugs which either bind glutathione (GSH) or prevent its synthesis. There appears to be a relationship between the synthesis of heat shock proteins and the induction of heat resistance. The effect of thiol modulation will be studied in the context of heat shock proteins. Recently, several compounds have been introduced which elevate cellular GSH. These compounds will be synthesized and evaluated in regard to thermal response.